Founder, Amp Discovery, LLC
On the Road to Commercialization of Antimicrobial Peptides to Treat Gram-Negative Bacterial Infections
There are now “Superbugs” that are resistant to all available antibiotics. We have designed de novo all D-conformation 26-residue amphipathic α-helical antimicrobial peptides (AMPs) that are effective against 7 strains of Acinetobacter baumannii resistant to antibiotics of last resort (colistin and polymyxin B) and 20 world-wide isolates from 2016 and 2017 with resistance to 18 different antibiotics. These isolates came from 4 continents, 12 different countries, and 17 different cities. Our AMPs have no toxicity as measured by the most stringent test of hemolysis of human red blood cells (18 hours at 37oC and up to 2000 µg/ml of AMP). We accomplished this by incorporation of unusual amino acids Dab and Dap into our peptides on the polar face to replace Lys residues and the use of two “specificity determinants” in the center of the non-polar face which provides specificity for prokaryotic cells over eukaryotic cells. These “specificity determinants” prevent unwanted high affinity binding to serum proteins as well as selectivity for Gram-negative organisms. This is the first successful demonstration of the use of Dab and Dap residues in AMPs. Our AMPs have excellent antimicrobial activity against antibiotic resistant organisms and the potential to be a new class of antibiotics where the development of resistance is highly unlikely due to their non-specific interaction with bacterial membranes.
Dr. Hodges has been Professor of Biochemistry and Molecular Genetics and the John Stewart Chair in Peptide Chemistry at the University of Colorado, Anschutz Medical Campus, Aurora, CO, for the past 20 years. He has a broad background in synthetic peptide chemistry having trained with Dr. Bruce Merrifield at Rockefeller University, a Nobel Laureate who developed solid-phase peptide chemistry. Dr. Hodges has successfully used this technology to study the structure and function of peptides and proteins, the feasibility of developing antimicrobial peptides with specificity for Gram-negative pathogens to developing synthetic peptide vaccines to α-helical B-cell epitopes in Type 1 fusion proteins of emerging and re-emerging viruses. He has won many awards. He is a Fellow of the Royal Society of Canada, the Vincent Du Vigneaud Award from the American Peptide Society for outstanding achievements in peptide/protein research and most recently the Bruce Merrifield Award for outstanding lifetime accomplishment in peptide research recognizing the highest level of scientific creativity in 2017.